Efforts at finding a successful chemotherapy for pancreatic cancer have been disappointing. Some patients are at increased risk of pancreatic cancer or may have pre-malignant pancreatic lesions which predispose them to later pancreatic cancer development. In these individuals, chemopreventative measures may block future development of pancreatic cancer. Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are precursors of pancreatic cancer. These precancerous lesions form inside the pancreatic ductal system and secrete a mucinous material. The malignant potential of IPMNs is thought to be a function of their degree of dysplasia. Our preliminary data suggests COX-2 expression and activity (PGE2 level) may indeed be associated with degree of dysplasia. Cyclooxygenase-2 appears to play a significant role in pancreatic tumorigenesis. The role of COX-2 inhibitors in IPMN has not been determined. We are conducting a biomarker study of celecoxib (COX-2 inhibitor) in patients with IPMN. Since IPMNs are intraductal lesions, we propose to examine IPMN biopsies and pancreatic ductal fluid pre- and post-celecoxib treatment to determine the effect of COX-2 inhibitors on COX-2 activity (PGE2 levels), COX-2 expression, dysplastic stage, and indices of proliferation, apoptosis and angiogenesis. We will also investigate celecoxib's effects on the expression of novel markers of IPMN malignant progression by cell block/immunocytochemistry ELISA and SELDI. Importantly, these studies may provide clinical evidence in support of a multi-institutional study of COX-2 inhibitors for chemoprevention in patients with IPMN and other precancerous pancreatic lesions at high risk for the development of pancreatic cancer. [unreadable] [unreadable] [unreadable]